| 1. |
- Ahmad, Abrar, 1984-, et al.
(författare)
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Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma
- 2015
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 11:4, s. 2493-2503
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Tidskriftsartikel (refereegranskat)abstract
- There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.
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| 2. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality : Results from a 6.7-year follow-up of a healthy community-living elderly population
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:6, s. 4629-4636
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.
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| 3. |
- Bu, Huajie, et al.
(författare)
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Genotype < 21CAs/>= 21CAs and allele < 21CAs of the MANBA gene in melanoma risk and progression in a Swedish population
- 2009
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Ingår i: Molecular medicine reports. - : Spandidos Publications Ltd.. - 1791-2997 .- 1791-3004. ; 2:2, s. 259-263
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.
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| 4. |
- El-Salhy, Magdy, et al.
(författare)
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Low density of ghrelin cells in the oxyntic mucosa correlated to slow gastric emptying in patients with type 1 diabetes
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2:6, s. 893-896
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a peptide hormone that has been isolated from the stomach and localized to endocrine cells in the oxyntic mucosa. Ghrelin acts synergistically with GH-releasing hormone and increases appetite and feeding. It also accelerates gastric and small intestinal motility in rodents. Patients with diabetes suffer from slow gastric emptying, giving rise to nausea and vomiting. The present study was undertaken to establish the possible role of ghrelin in slow gastric emptying observed in patients with longstanding type 1 diabetes, and to correlate the results with the metabolic status of these patients. Eleven patients with type 1 diabetes along with 10 and 15 healthy volunteers as controls underwent gastrointestinal endoscopy/biopsy or gastric scintigraphy. Gastric emptying in patients and controls was measured by scintigraphy. Sections from biopsies of the oxyntic mucosa and duodenum were immunostained for ghrelin with the avidin-biotin complex method. The density of the cells was quantified with computerized image analysis. Both the lag phase and half-emptying time (T-50) were higher in patients with diabetes than in healthy volunteers. The T-50 was correlated with the blood glucose level. The density of ghrelin-immunoreactive cells in the oxyntic mucosa of patients with diabetes was significantly reduced compared to the healthy controls. Ghrelin cell density was correlated with both the lag phase and T-50, as well as with blood glucose level. The present finding of reduced density of ghrelin cells in patients with type 1 diabetes, which was well correlated with gastric emptying, indicates the possible role of ghrelin in the pathophysiology of gastroparesis observed in diabetes.
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| 5. |
- Eriksson, Staffan
(författare)
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Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2, s. 923-929
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Tidskriftsartikel (refereegranskat)abstract
- Thymidine kinase 1 (TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 and PCNA in breast, lung and colorectal carcinoma. In this study, we extend the work of prior breast carcinoma studies by investigating the expression of TK1 in 132 patients with usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). TK1 and Ki-67 expression were determined with monoclonal antibodies using the SP technique. The expression of TK1 was found to be significantly increased in the breast ductal carcinomas in the following manner: UDH
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| 6. |
- Erlandson, Anna, et al.
(författare)
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Epigenetic mutations in CDKN2A in western Swedish families with hereditary malignant melanoma
- 2008
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Ingår i: Molecular Medicine Reports. - Athens, Greece : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 1:1, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify the molecular genetic variations associated with an increased risk of hereditary malignant melanoma (HMM) in the western Swedish population. In 68 families with increased hereditary susceptibility to malignant melanoma, we previously reported a low frequency of alterations in the CDKN2A gene, which is regarded as the major melanoma predisposition gene. Among these alterations, we identified a novel mutation in 3 families (Asp108Tyr). In the present study, we focused on the possible role of heritable epimutations as a cause of the silencing of the CDKN2A gene. We used two different technical approaches to detect changes in CpG methylation in the promoter region of the CDKN2A gene; methylation-specific PCR (MSP) analysis of bisulfite-converted DNA and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). From families who tested negative for germ-line CDKN2A mutations, 64 unrelated patients with hereditary melanoma were included in the study. We showed a consistent lack of hypermethylation in the promoter region of CDKN2A in patients with HMM in our western Swedish population. A putative germ-line methylation of the CDKN2A, if any, is therefore likely to be a rare event in hereditary melanoma. This study demonstrates that there are probably additional and as yet unknown genetic factors present in western Swedish HMM families.
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| 7. |
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| 8. |
- Fragkiadaki, Persefoni, et al.
(författare)
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Telomerase inhibitors and activators in aging and cancer : A systematic review
- 2022
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 25:5
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Forskningsöversikt (refereegranskat)abstract
- The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.
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| 9. |
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| 10. |
- Jönsson, Anette, et al.
(författare)
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Long‑term follow‑up of buserelin‑induced enteric neuropathy in rats.
- 2016
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 13:4, s. 3507-3513
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Tidskriftsartikel (refereegranskat)abstract
- A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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| 11. |
- Kalikstad, Betty, et al.
(författare)
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Gene expression profiles in preterm infants on continuous long-term oxygen therapy suggest reduced oxidative stress-dependent signaling during hypoxia
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 15:4, s. 1513-1526
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Tidskriftsartikel (refereegranskat)abstract
- Preterm infants are susceptible to neonatal inflammatory/ infective diseases requiring drug therapy. The present study hypothesized that mRNA expression in the blood may be modulated by signaling pathways during treatment. The current study aimed to explore changes in global gene expression in the blood from preterm infants with the objective of identifying patterns or pathways of potential relevance to drug therapy. The infants involved were selected based on maternal criteria indicating increased risk for therapeutic intervention. Global mRNA expression was measured in 107 longitudinal whole blood samples using Affymetrix Human-Genome-U133 Plus 2.0-arrays; samples were obtained from 20 preterm infants. Unsupervised clustering revealed a distinct homogeneous gene expression pattern in 13 samples derived from seven infants undergoing continuous oxygen therapy. At these sampling times, all but one of the seven infants exhibited severe drops in peripheral capillary saturation levels below 60%. The infants were reoxygenated with 100% inspired oxygen concentration. The other samples ( n= 94) represented the infants from the cohort at time points when they did not undergo continuous oxygen therapy. Comparing these two sets of samples identified a distinct gene expression pattern of 5,986 significantly differentially expressed genes, of which 5,167 genes exhibited reduced expression levels during transient hypoxia. This expression pattern was reversed when the infants became stable, i. e., when they were not continuously oxygenated and had no events of hypoxia. To identify signaling pathways involved in gene regulation, the Database for Annotation, Visualization and Integrated Discovery online tool was used. Mitogen-activated protein kinases, which are normally induced by oxidative stress, exhibited reduced gene expression during hypoxia. In addition, nuclear factor erythroid 2-related factor 2-antioxidant response element target genes involved in oxidative stress protection were also expressed at lower levels, suggesting reduced transcription of this pathway. The findings of the present study suggest that oxidative stress-dependent signaling is reduced during hypoxia. Understanding the molecular response in preterm infants during continuous oxygenation may aid in refining therapeutic strategies for oxygen therapy.
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| 12. |
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| 13. |
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| 14. |
- Lundmark, Fanny, et al.
(författare)
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Reduction of renal activity retention of radiolabeled albumin binding domain-derived affinity proteins using a non-residualizing label strategy compared with a cleavable glycine-leucine-glycine-lysine-linker
- 2024
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of targeted imaging and therapy using radiolabeled albumin-binding domain-derived affinity proteins (ADAPTs) has been demonstrated. However, high renal uptake of radioactivity limits the maximum tolerated dose. Successful reduction of renal retention of radiolabeled Fab fragments has been demonstrated by incorporating a cleavable linker between the targeting agent and the radiometal chelator. The present study investigated if the introduction of a glycine-leucine-glycine-lysine (GLGK)-linker would reduce the kidney uptake of radiolabeled ADAPT6 and also compared it with the non-residualizing [125I]I-[(4-hydroxyphenyl)ethyl]maleimide ([125I]I-HPEM) labeling strategy. GLGK was site-specifically coupled to human epidermal growth factor receptor 2 (HER2)-targeting ADAPT6. Conjugates without the cleavable linker were used as controls and all constructs were labeled with lutetium-177 (177Lu). [125I]I-HPEM was coupled to ADAPT6 at the C-terminus. Biodistribution of all constructs was evaluated in NMRI mice 4 h after injection. Specific binding to HER2-expressing cells in vitro was demonstrated for all constructs. No significant difference in kidney uptake was observed between the [177Lu]Lu-2,2 ',2",2"'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid-GLGK-conjugates and the controls. The renal activity of [125I]I-HPEM-ADAPT6 was significantly lower compared with all other constructs. In conclusion, the incorporation of the cleavable GLGK-linker did not result in lower renal retention. Therefore, the present study emphasized that, in order to achieve a reduction of renal retention, alternative molecular design strategies may be required for different targeting agents.
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| 15. |
- Luo, Cheng, et al.
(författare)
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Molecular inhibition mechanisms of cell migration and invasion by coix polysaccharides in A549 NSCLC cells via targeting S100A4
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 15:1, s. 309-316
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Tidskriftsartikel (refereegranskat)abstract
- S100 calcium binding protein A4 (S100A4) promotes extracellular signal transduction, intercellular adhesion, motility and mobility. Different extracts from Coix lachryma-jobi have been used for the treatment of various types of cancer in Asia. In our previous study, the polysaccharide fraction extact, CP1, induced cell apoptosis of non-small cell lung cancer cells. In the current study, CP1 inhibited migration and invasion of A549 cells in a scratch wound healing assay and matrigel invasion assay, respectively. Furthermore, reverse transcription-polymerase chain reaction and western blotting demonstrated that CP1 downregulated the gene and protein expression levels of SI00A4. In silico docking analysis demonstrated that polysaccharides may not interfere with dimerization, whereas, the affinity of polysaccharides for an S100A4-NMIIA pocket was margnially greater than at the dimerization sites. Thus, CP1 inhibited A549 cell migration and invasion potentially via downregulation of S100A4, and may also interact with the binding site of S100A4-NMIIA, which indicated that CP1 has potential as an alternative cancer chemotherapeutic by targeting S100A4.
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| 16. |
- Mälarstig, Anders, et al.
(författare)
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Tumour-derived adhesion factor in colorectal cancer
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2:6, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Tumour-derived adhesion factor (TAF) has been shown to be associated with breast, prostate and colorectal cancer (CRC), acting as tumour suppressor or tumour promoter by mechanisms not as yet understood. Here, we comparatively analyzed the expression profile of TAF in plasma, tumour and paired normal tissue from patients with CRC. In addition, we investigated the relationship between TAF and systemic inflammation, mirrored by the elevation of interleukin-6 (IL-6) and TAF levels in plasma. Levels of TAF and IL-6 were determined by ELISA. Immunohistochemistry was performed to investigate the site of TAF expression. We also used a TaqMan system to investigate a TAF single nucleotide polymorphism (rs2041437) with a potential effect on CRC. TAF protein levels were significantly (Pless than0.001) higher in colorectal tumours than in normal tissue, and were increased in patients with Dukes stages B and C compared to A. Immunohistochemistry revealed heterogeneous TAF expression mainly in the epithelial cells of the cancer and normal tissue. The plasma TAF level was reduced in CRC patients compared with the controls (P=0.002), independent of the inflammatory marker IL-6. Regarding genotype and allelic distributions, significant differences between CRC patients and control subjects or associations between clinical characteristics and TAF levels in tissue and plasma were not observed. In conclusion, altered TAF protein expression in cancer tissue may be a potential biomarker in colorectal carcinogenesis. Further research exploring the regulation of TAF is required to evaluate whether TAF is linked to clinical outcome.
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| 17. |
- Nilsson, Torbjörn K., et al.
(författare)
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MTHFR polymorphisms and serum cobalamin affect plasma homocysteine concentrations differentially in females and males
- 2014
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 10:5, s. 2706-2712
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Tidskriftsartikel (refereegranskat)abstract
- A total of 523 subjects (297 females and 226 males) from the Canary Islands Nutrition Study (ENCA) were studied in order to examine the effect of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms, adjusted for age, serum (5)-folate and S-cobalamin levels, on total plasma homocysteine concentrations (tHcy). Genotyping was performed with Pyrosequencing(R) technology. The MTHFR 677T-allele was associated with increased tHcy concentrations only in males (P=0.005). The MTHFR 1298C-allele was found to be associated with higher tHcy levels but similarly, only in males (P=0.025). The MTHFR 1793A-allele was associated with decreased tHcy concentrations in the younger males (P=0.042). A haplotype-based approach was marginally superior in explaining the genetic interaction of the MTHFR polymorphisms on tHcy plasma levels (R-2 0.352 vs. 0.342 for a simple genotype-based approach). A nutrigenetic interaction between the MTHFR 677C>T genotype and S-cobalamin on tHcy levels was demonstrated in both genders. The increase in tHcy was more pronounced with decreasing S-cobalamin quintiles in 677TT homozygotes (P=0.005 for males and P=0.015 for females) than with decreasing S-folate quintiles (P for trend not significant). It was concluded that gene-nutrient interactions may differ depending on the sex and age of the subjects. The transferability of gene-nutrient interactions from one community to others may therefore be limited not only by different food patterns but also by different ages, genders and genotype distributions.
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| 18. |
- Ohlsson, Bodil
(författare)
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Functional bowel symptoms in the general population (Review)
- 2022
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 26:1
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Forskningsöversikt (refereegranskat)abstract
- Several patients with irritable bowel syndrome (IBS) do not seek medical attention for their symptoms. When patients with IBS seek help, the majority of them are handled at primary healthcare centers, whereas research studies are performed at tertiary healthcare centers. The present study aimed to summarize findings from >4,000 participants of the general population included in the Malmö Offspring Study (inclusion rate 46.7%). The participants were clinically examined, their blood and fecal samples collected, and their questionnaires completed. The participants were divided into subjects with or without self?reported IBS and those having functional gastrointestinal (GI) symptoms in the past 2 weeks. The presence of IBS and GI symptoms in the participants were associated with each other. Zonulin levels did not differ between participants with or without GI diseases and were not associated with the degree of GI symptoms. The parameters low body weight at birth and small for gestational age were associated with the degree of the symptoms' influence on daily life. IBS and GI symptoms were positively associated with Blautia abundance. Beta?diversity differed between participants with or without these two conditions. Positive correlations were noted between the degree of diarrhea and the mean 24?h measurements of systolic blood pressure, diastolic blood pressure, and heart rate. Both IBS and GI symptoms were associated with female sex, smoking, stress, poor sleeping habits, unemployment, drug use, and a family history of GI diseases, whereas younger age was inversely associated with IBS and its associated symptoms. In conclusion, only a limited number of medical findings could be identified in participants with IBS and GI symptoms, whereas sociodemographic and environmental conditions were associated with these entities.
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| 19. |
- Ohlsson, Bodil
(författare)
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Theories behind the effect of starch‑ and sucrose‑reduced diets on gastrointestinal symptoms in irritable bowel syndrome (Review)
- 2021
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 24:4
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Forskningsöversikt (refereegranskat)abstract
- increased amounts of starch and sugar have been added to the diet in the Western world during the last decades. undigested carbohydrates lead to bacterial fermentation and gas production with diffusion of water, causing abdominal bloating, pain and diarrhea. Therefore, dietary advice is the first line of treatment of irritable bowel syndrome (IBS), a disease characterized by abdominal pain and altered bowel habits without any organic findings. recently, a diet with a reduction of starch and sucrose led to a marked effect on gastrointestinal (GI) symptoms. The mechanism is unknown, but three possible mechanisms are presented in the present review. First, functional variants of the enzyme sucrase‑isomaltase (SI) have been described in IBS. A subgroup of patients with IBS may thus suffer from partial SI deficiency with reduced digestion of starch and sucrose. Second, fructose absorption is less efficient than glucose absorption, which may lead to a physiological fructose malabsorption when ingesting high amounts of sucrose. a third mechanism is that high‑sugar diets causing hypergly‑ cemia, hyperinsulinemia and weight gain have led to painful neuropathy in animal models; whereas, improved metabolic control in humans has led to improvement of neuropathy. Starch‑ and sucrose‑reduced diets lead to decreased levels of c‑peptide, insulin, gastric inhibitory peptide, leptin and weight reduction. These metabolic changes may reduce the excitability of the hypersensitive nervous system often found in IBS and, thereby, lead to the reduced symptoms found after the diet. in conclusion, further studies are needed to investi‑ gate the pathophysiology behind development of symptoms after starch and sucrose intake, and the mechanisms behind symptom relief after reduced intake.
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| 20. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Prenatal essential fatty acid deficiency in mice results in long-term gender-specific effects on body weight and glucose metabolism
- 2011
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 4:4, s. 731-737
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Tidskriftsartikel (refereegranskat)abstract
- Essential fatty acids are important for normal growth and development in early life. However, the long-term effects of prenatal essential fatty acid deficiency (EFAD) on the adult metabolism remain to be determined. The aim of this study was to investigate the effects of an EFAD diet given to mice during late gestation on body weight and body composition, and metabolism in the adult offspring. Pregnant dams were given an EFAD or a control diet during the last 10 days of gestation. After delivery, all mice were fed normal chow and the body weight of the offspring was measured weekly. Furthermore, food intake, energy expenditure and intraperitoneal glucose tolera-nce were analysed in the adult offspring in addition to body composition (analysed by dual-energy X-ray absorptiometry), plasma levels of leptin, triglycerides and cholesterol. The body weight was lower in the EFAD offspring as compared to the controls during the first 4 weeks of age, and remained lower in the females throughout the study. Lean body mass and plasma leptin levels were also lower in the female EFAD offspring as compared to the controls. Male EFAD offspring were found to have higher fasting glucose and insulin levels as well as higher insulin levels during the glucose tolerance test compared to the controls. However, no differences were found in blood lipids, food intake or energy expenditure between EFAD and control mice of either gender. These results demonstrate that an EFAD diet given during the last 10 days of gestation results in long-term gender-specific effects on body weight and insulin sensitivity in the adult offspring.
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| 21. |
- Pan, Lili, et al.
(författare)
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Expression of flTF and asTF splice variants in various cell strains and tissues
- 2019
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 19:3, s. 2077-2086
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Tidskriftsartikel (refereegranskat)abstract
- Tissue factor (TF) expressed at the protein level includes two isoforms: The membrane‑bound full‑length TF (flTF) and the soluble alternatively spliced TF (asTF). flTF is the major thrombogenic form of TF, whereas asTF is more closely associated with tumor growth, angiogenesis, metastasis and cell growth. In order to further investigate the different expression and functions of TF splice variants, the expression of these two splice variants were detected in numerous cell strains and tissues in the present study. Quantitative polymerase chain reaction was used to measure the transcript levels of the TF variants in 11 human cell lines, including cervical cancer, breast cancer, hepatoblastoma, colorectal cancer and umbilical vein cells, and five types of tissue specimen, including placenta, esophageal cancer, breast cancer, cervical cancer (alongside normal cervical tissues) and non‑small cell lung cancer (alongside adjacent and normal tissues). Furthermore, the effects of chenodeoxycholic acid (CDCA) and apolipoprotein M (apoM) on the two variants were investigated. The results demonstrated that flTF was the major form of TF, and the mRNA expression levels of flTF were higher than those of asTF in all specimens tested. CDCA significantly upregulated the mRNA expression levels of the two variants. Furthermore, overexpression of apoM promoted the expression levels of asTF in Caco‑2 cells. The mRNA expression levels of asTF in cervical cancer tissues were significantly higher than in the corresponding normal tissues. To the best of our knowledge, the present study is the first to compare the expression of flTF and asTF in various samples. The results demonstrated that CDCA and apoM may modulate TF isoforms in different cell lines, and suggested that asTF may serve a role in the pathophysiological mechanism underlying cervical cancer development. In conclusion, the TF isoforms serve important and distinct roles in pathophysiological processes.
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| 22. |
- Paramel, Geena, 1985-, et al.
(författare)
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Polymorphism in the NLRP3 inflammasome-associated EIF2AK2 gene and inflammatory bowel disease
- 2015
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 11:6, s. 4579-4584
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is the common name for numerous relapsing inflammatory conditions, and is the collective name for Crohn's disease (CD) and ulcerative colitis (UC). The activation of the inflammasome in the pathogenesis of IBD has recently been identified, however the underlying mechanisms remain unclear. An activator of the inflammasome is double-stranded RNA-dependent protein kinase R, also termed EIF2AK2. A genetic alteration in the EIF2AK2 gene has previously been shown to be associated with Alzheimer's disease. The present study genotyped samples from a Swedish cohort of patients with IBD and healthy controls for an EIF2AK2 polymorphism. The rs2254958 polymorphism in the 5'-untranslated region of the EIF2AK2 gene was genotyped by TaqMan® single nucleotide polymorphism genotyping, followed by allelic discrimination. However, no significant association was determined between the rs2254958 polymorphism and the development of IBD, or clinical outcome. In conclusion, the results of the present study suggest that the rs2254958 polymorphism has a limited effect on the onset or progression of IBD.
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| 23. |
- Portelius, Erik, 1977, et al.
(författare)
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The amyloid-β isoform pattern in cerebrospinal fluid in familial PSEN1 M139T- and L286P-associated Alzheimer's disease
- 2012
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 5:4, s. 1111-1115
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Tidskriftsartikel (refereegranskat)abstract
- There are several familial forms of Alzheimer's disease (AD) most of which are caused by mutations in the genes that encode the presenilin enzymes involved in the production of amyloid-β (Aβ) from the amyloid precursor protein (APP). In AD, Aβ forms fibrils that are deposited in the brain as plaques. Much of the fibrillar Aβ found in the plaques consists of the 42 amino acid form of Aβ (Aβ1-42) and it is now widely accepted that Aβ is related to the pathogenesis of AD and that Aβ may both impair memory and be neurotoxic. In human cerebrospinal fluid (CSF) several C- and N-terminally truncated Aβ isoforms have been detected and their relative abundance pattern is thought to reflect the production and clearance of Aβ. By using immunoprecipitation and mass spectrometry, we have previously demonstrated that carriers of the familial AD (FAD)-associated PSEN1 A431E mutation have low CSF levels of C-terminally truncated Aβ isoforms shorter than Aβ1-40. Here we replicate this finding in symptomatic carriers of the FAD-causing PSEN1 L286P mutation. Furthermore, we show that preclinical carriers of the PSEN1 M139T mutation may overexpress Aβ1-42 suggesting that this particular mutation may cause AD by stimulating γ-secretase-mediated cleavage at amino acid 42 in the Aβ sequence.
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| 24. |
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| 25. |
- Shi, Yuanping, et al.
(författare)
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Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide‑induced acute inflammatory apoM‑/‑ mice
- 2020
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3117-3126
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Tidskriftsartikel (refereegranskat)abstract
- apolipoproteinM(apoM)mayserveaprotectiverole inthedevelopmentofinflammation.Nuclearfactor‑κB(nF-κB) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)‑induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM‑knockout mouse model. The levels of inducible nitric oxide synthase (iNOS), NF‑κB, interleukin (IL)‑1β, intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion protein 1 (VCAM‑1) were detected using reverse transcription‑quantitative PCR and western blotting. The serum levels of IL‑6 and IL‑10 were detected using Luminex technology. The results demonstrated that the protein levels of inoS, nF-κB, il-1β, ICAM‑1 and VCAM‑1 were significantly increased in apoM-/- mice compared with those in apoM+/+ mice. In addition, two‑way ANOVA revealed that the interaction between apoM and LPS had a statistically significant effect on a number of factors, including the mRNA expression levels of hepatic iNOS, NF‑κB, il-1β, icaM-1 and VCAM‑1. Notably, the effects of apoM and 10 mg/kg LPS on the levels of IL‑6 and IL‑10 were the opposite of those induced by 5 mg/kg LPS, which could be associated with the dual anti‑ and pro‑inflammatory effects of IL‑6 and IL‑10. Collectively, the results of the present study revealed that apoM is an important regulator of inflammatory cytokine and adhesion molecule production in LPS‑induced inflammation, which may consequently be associated with the severity of inflammation. These findings indicated that the anti‑inflammatory effects of apoM may partly result from the inhibition of the nF-κB pathway.
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| 26. |
- Sjölander, Annica, 1969, et al.
(författare)
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Alzheimer's disease: No effect of the CDK5 gene on CSF biomarkers, neuropathology or disease risk
- 2009
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 2:6, s. 989-992
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin-dependent kinase 5 (cdk5) has been identified as one of the kinases that phosphorylates tau at several Alzheimer's disease (AD)-associated sites. Cdk5 is predominantly expressed in neurons, and has higher activity in AD brains than in non-demented brains. To investigate the effect of the CDK5 gene on AD, we analyzed an SNP of the CDK5 gene (rs2069456) in 347 patients with AD and in 157 controls. CDK5 genetic data was investigated in subgroups in relation to biochemical and neuropathological markers for AD. We found no significant differences in genotype or allele distributions between AD patients and controls. None of the CDK5 gene variants influenced biomarkers for AD.
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| 27. |
- Vazquez-Sanchez, Ernesto A., et al.
(författare)
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Heptapeptide HP3 acts as a potent inhibitor of experimental imiquimod-induced murine psoriasis and impedes the trans-endothelial migration of mononuclear cells
- 2020
-
Ingår i: Molecular Medicine Reports. - : SPANDIDOS PUBL LTD. - 1791-2997 .- 1791-3004. ; 22:1, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- During the progression of psoriatic lesions, abundant cellular infiltration of myeloid cells, such as macrophages and activated dendritic cells, occurs in the skin and the infiltrating cells interact with naive lymphoid cells to generate a T helper (Th)1 and Th17 environment. Therapies to treat psoriasis include phototherapy, non-steroidal and steroidal drugs, as well as antibodies to block tumor necrosis factor-alpha, interleukin (IL)-17-A and IL-12/IL-23, which all focus on decreasing the proinflammatory hallmark of psoriasis. The present study obtained the heptapeptide HP3 derived from phage display technology that blocks mononuclear cell adhesion to endothelial cells and inhibits trans-endothelial migrationin vitro. The activity of the heptapeptide in a murine model of psoriasis was also assessed, which indicated that early administration inhibited the development of psoriatic lesions. Therefore, the results suggested that HP3 may serve as a potential therapeutic target for psoriasis.
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| 28. |
- Vorkapic, Emina, et al.
(författare)
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Effects of osteoprotegerin/TNFRSF11B in two models of abdominal aortic aneurysms
- 2018
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Ingår i: Molecular Medicine Reports. - : SPANDIDOS PUBL LTD. - 1791-2997 .- 1791-3004. ; 18:1, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG), additionally termed tumor necrosis factor receptor superfamily member 11B, is produced by vascular smooth muscle cells (VSMCs) and endothelial cells in the vasculature, and its release may be modulated by pro-inflammatory cytokines, including nterleukin-1 beta and tumor necrosis factor-alpha. The present study investigated the effects of treatment with low-dose human recombinant OPG on abdominal aortic aneurysm (AAA) development in mice. Mice were treated with 1 mu g human recombinant OPG four times (or vehicle) for 2 weeks prior to inducing AAA. A total of two different models for inducing AAA were used to investigate the hypothesis as to whether OPG is involved in key events of AAA development, using osmotic mini-pumps with angiotensin II in apolipoprotein-E (ApoE(-/-)) mice for 28 days or using periaortic application of CaCl2 on the aorta in C57131/6J mice for 14 days. OPG was continuously administered during the experimental period. Histological staining using Massons trichrome, Verhoeffs van-Gieson and picro-sirius red, in addition to reverse transcription-quantitative polymerase chain reaction analysis of various markers, were used to analyze phenotypic alterations. Treatment with OPG had no inhibitory effect on AAA development in the angiotensin II model in ApoE(-/-) mice, which developed suprarenal aneurysms, although it increased vessel wall thickness of the aorta and total collagen in C57B116J mice using the CaCl2 model that induced infrarenal dilation of the aorta. Treatment with OPG did not inhibit aneurysm development and key events, induding inflammation, extracellular matrix or VSMC remodeling, in aortas from OPG-treated mice with periaortic treatment with CaCl2. The results indicated that mice treated with low levels of human recombinant OPG may have a more stable aneurysmal phenotype due to compensatory production of collagen and increased vessel wall thickness of the aorta, potentially protecting the aneurysm from rupture. Further studies investigating rupture models of AAA in addition to using higher levels of OPG are require to verify this speculation. Furthermore, treatment with low levels of OPG in patients with AAA may represent a novel therapeutic strategy for the treatment of AAA as well as attenuate the adverse effects associated with the administration of normal and high dosages of OPG.
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| 29. |
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| 30. |
- Wågsäter, Dick, et al.
(författare)
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Quantification of the chemokines CCL17 and CCL22 in human colorectal adenocarcinomas
- 2008
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 1:2, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines are believed to play a crucial role in local immunoresponse by regulating leukocyte movement in various tissues, including the intestinal mucosa. It has been suggested that they are key players in cancer biology, and several studies have identified leukocyte infiltration as a hallmark of most cancers. The chemokines CCL17 and CCL22 attract CCR4-bearing cells, which are especially polarised to Th2-type cells and regulatory T cells (Treg). Recent studies have revealed the participation of the CCL17 and CCL22 proteins in diseases such as atopic dermatitis and lymphoma. The purpose of this study was to assess the role of CCL17 and CCL22 protein expression in colorectal cancer (CRC) and to ascertain whether an association exists between promoter -431Cgreater thanT CCL17 and -961Ggreater thanA CCL22 gene polymorphisms in CRC versus non-CRC subjects. Using the ELISA assay, we noted a significantly higher expression of CCL22 in tumour tissue with a 2.3-fold up-regulation (tumour vs. paired normal tissue, n=78) but no significant difference in CCL17 protein expression. Immunohistochemistry revealed protein expression of CCL22 and CCL17 in the epithelial compartment of cancer tissue, in epithelial cells at the resection border that reflects normal tissue, and in some stromal cells such as lymphocytes, macrophages, and fibroblasts. Using a TaqMan system we screened for -431Cgreater thanT CCL17 and -961Ggreater thanA CCL22 gene variants in 245 CRC patients and 256 controls, but could not find any significant difference in genotype distribution or in allelic frequencies between the two groups. The genotype and allelic distributions of CRC patients were not related to tissue levels of CCL17 and CCL22 protein, and none of the variables were associated with plasma levels or clinical characteristics. To ascertain whether the tissue expression of CCL17 and CCL22 exerts an influence oil the pathogenesis of CRC, a forthcoming study oil the 5-year survival rate of CRC patients will be conducted.
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| 31. |
- Yu, Miao mei, et al.
(författare)
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Apolipoprotein M increases the expression of Vitamin D receptor mRNA in colorectal cancer cells detected with duplex fluorescence reverse transcription-quantitative polymerase chain reaction
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 16:2, s. 1167-1172
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (ApoM) and the Vitamin D receptor (VDR) are apolipoproteins predominantly presenting in high-density lipoprotein (HDL) and a karyophilic protein belonging to the steroid-thyroid receptor superfamily, respectively. Previous studies have demonstrated that ApoM and VDR are associated with cholesterol metabolism, immune and colorectal cancer regulation. In order to investigate whether ApoM affected the expression of VDR in colorectal cancer cells, a single-tube duplex fluorescence reverse transcription-quantitative polymerase chain reaction (RT-qPCR) system was developed to simultaneously detect the mRNA levels of VDR and GAPDH in HT-29 cells overexpressing ApoM. The results demonstrated that the amplification products were confirmed as the specific fragment of VDR/GAPDH using the DNA sequencing instrument. The sensitivity, linear range, correlation coefficient, amplification efficiency, intra-assay and inter-assay coefficients of variation were 40 copies/μl, 4.00×101-4.00×105 copies/μl, 0.999, 92.42%, 0.09-0.34% and 0.32-0.65% for VDR, and 40 copies/μl, 400×101-4.00×105 copies/μl, 0.999, 98.07%, 0.19-0.43% and 0.40-0.75% for GAPDH, respectively. The results indicated that the expression of VDR mRNA was significantly higher in HT-29 cells overexpressing ApoM, compared with the negative control group (P<0.05). In conclusion, the current study successfully developed the single-tube duplex RT-qPCR to simultaneously detect VDR and GAPDH expression in colorectal cancer cells. The methodology results demonstrated that the duplex RT-qPCR system with high sensitivity and specificity could ensure the objectivity and credibility of the detection. The present study confirmed that ApoM significantly increased the expression of VDR in HT-29 cells. In addition, it was hypothesized that ApoM may be involved in antineoplastic activity via the upregulation of VDR expression, which may provide novel directions for the investigation of ApoM in cancer.
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| 32. |
- Zhang, Yi, et al.
(författare)
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Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 16:1, s. 794-800
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Tidskriftsartikel (refereegranskat)abstract
- Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.
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| 33. |
- Zhu, Zhechen, et al.
(författare)
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Association between the ABCC11 gene polymorphism and the expression of apolipoprotein D by the apocrine glands in axillary osmidrosis.
- 2015
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 11:6, s. 4463-4467
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the adenosine triphosphate‑binding cassette sub‑family C member 11 (ABCC11) gene polymorphism and apolipoprotein D (ApoD), an odor precursor carrier, may be important in the formation of axillary odor. To date, few studies have examined the potential correlation between these two factors. The present study aimed to investigate the association between a 538 G>A single‑nucleotide polymorphism (SNP) of the ABCC11 gene and the mRNA expression levels of ApoD in the apocrine gland of patients with osmidrosis. The 538 G>A polymorphism genotypes of 33 patients with a clinical diagnosis of osmidrosis were analyzed by polymerase chain reaction (PCR) and a base‑quenched probe method, and they were divided into two groups according to the results. The G allele functions as a dominant gene; therefore, patients with the GG or GA genotype were allocated to Group I (n=28) and patients with the AA genotype to Group II (n=5). The mRNA expression levels of ApoD in the apocrine glands were determined by reverse transcription‑PCR. The results indicated that the mRNA expression levels of ApoD were significantly higher in the apocrine glands of patients in Group I compared with those in Group II (P<0.01). In conclusion, the results indicated that the ABCC11 gene SNP of the 538 G>A allele was associated with a downregulation of the mRNA expression of ApoD in the apocrine glands, which may indicate a role for the ABCC11 gene in the mediation of osmidrosis by enhancing the transition of odor precursors via the ApoD pathway.
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| 34. |
- Zhu, Ziqiang, et al.
(författare)
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Integrative microRNA and mRNA expression profiling in acute aristolochic acid nephropathy in mice
- 2020
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3367-3377
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Tidskriftsartikel (refereegranskat)abstract
- In acute aristolochic acid nephropathy (AAN), aristolochic acid (AA) induces renal injury and tubulointerstitial fibrosis. However, the roles of microRNAs (miRNAs/miRs) and mRNAs involved in AAN are not clearly understood. The aim of the present study was to examine AA-induced genome-wide differentially expressed (DE) miRNAs and DE mRNAs using deep sequencing in mouse kidneys, and to analyze their regulatory networks. In the present self-controlled study, mice were treated with 5 mg/kg/day AA for 5 days, following unilateral nephrectomy. AA-induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. A total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the AA-treated group and the self-control group. Of these DE miRNAs and mRNAs, some were validated using reverse transcription-quantitative PCR. Expression levels of the profibrotic miR-21, miR-433 and miR-132 families were significantly increased, whereas expression levels of the anti-fibrotic miR-122-5p and let-7a-1-3p were significantly decreased. Functions and signaling pathways associated with the DE miRNAs and mRNAs were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 767 DE pairs (in opposing directions) of miRNAs and their mRNA targets were identified. Among these, regulatory networks of miRNAs and mRNAs were analyzed using KEGG to identify enriched signaling pathways and extracellular matrix-associated pathways. In conclusion, the present study identified genome-wide DE miRNAs and mRNAs in the kidneys of AA-treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of DE miRNAs and their mRNA targets in the pathophysiology of acute AAN.
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| 35. |
- Cheng, Junping, et al.
(författare)
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The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36
- 2010
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 3:1, s. 155-160
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Tidskriftsartikel (refereegranskat)abstract
- Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.
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| 36. |
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| 37. |
- Ha, Chunfang, et al.
(författare)
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Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia
- 2009
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 2:1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (>= 80 ml per menstruation) and 12 women with normal blood loss (<80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p<0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.
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| 38. |
- Isaksson-Mettävainio, Martin, et al.
(författare)
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c-Met expression in primary tumors and their corresponding distant metastases
- 2009
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Ingår i: Molecular Medicine Reports. - Umeå : Spandidos Publications. - 1791-2997. ; 1:6, s. 787-790
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Tidskriftsartikel (refereegranskat)abstract
- c-Met is a receptor tyrosine kinase that has beenimplicated in the pathogenesis and growth of a wide variety ofhuman malignancies, including CRC, but its role in metastasisis largely unknown. We compared c-Met expression in primaryhuman colorectal carcinomas and distant metastases from thesame patients. Formalin-fixed paraffin-embedded tissuesamples from 69 colorectal cancer patients were obtained. Theprotein expression of c-Met was evaluated immunohistochemicallyusing a commercial antibody. The difference inexpression between primary tumors and their correspondingdistant metastases was analyzed using the Wilcoxon signedranktest. c-Met expression was statistically significantlylower in the distant metastases compared to their correspondingprimary tumors (p<0.001), whereas no difference was foundbetween lymph node metastases and their correspondingprimary tumors (p=0.957). The degree of c-Met expressionwas not related to clinicopathological characteristics such astumor grade and Dukes' stage at the time of primary tumordiagnosis, or to the location of the distant metastases. Wedemonstrated that c-Met expression is often reduced in distantmetastases compared to their corresponding primary colorectaltumors. Additional studies of c-Met activation and signaltransduction will increase our knowledge about the role ofc-Met in colorectal cancer metastasis.
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| 39. |
- Lewander, Andreas, et al.
(författare)
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Polymorphism in the promoter region of the NFKBIA gene is rare in Swedish and Chinese colorectal cancer patients and controls
- 2010
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Ingår i: MOLECULAR MEDICINE REPORTS. - : Spandidos Publications. - 1791-2997. ; 3:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether a -708ins/del8 polymorphism in the promoter region of the NFKBIA gene is related to colorectal cancer risk and clinicopathological variables, we, genotyped 92 Swedish and 93 Chinese patients as well as 174 Swedish and 159 Chinese healthy controls by polymerase chain reaction-single stranded conformation polymorphism and DNA sequencing. The -708/del8 polymorphism was found in two Swedish patients and eight Swedish controls, but was absent in the Chinese population. However, among the Chinese population we found other mutations in three patients and in one control. In conclusion, the -708ins/del8 polymorphism is too rare to have a major impact on colorectal cancer incidence in the two populations.
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| 40. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Novel cerebrospinal fluid biomarkers of axonal degeneration in frontotemporal dementia.
- 2008
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Ingår i: Molecular medicine reports. - : Spandidos Publications. - 1791-2997. ; 1:5, s. 757-61
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a heterogeneous disease with substantial interpersonal variance in aggressiveness. Novel biomarkers for rapidly progressive FTD could improve diagnosis and provide clues regarding its pathogenesis. In this study, surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to analyze peptide profiles in cerebrospinal fluid (CSF) from 24 FTD patients. Thirteen patients had rapidly progressive FTD with distinct pathology in a brain MRI after less than 3 years of disease duration. Eleven patients had slowly progressive FTD with a normal brain MRI, but had abnormal findings in SPECT/PET after more than 5 years of disease duration. The axonal damage marker CSF neurofilament light-chain (NF-L) was measured in all subjects to evaluate the amount of axonal degeneration. A CSF NF-L level of 150 ng/l was used as a cut-off point for high NF-L expression. SELDI-TOF analysis of peptides in the range of 2000-20000 m/z revealed one peak with m/z of 6378 that was expressed at a significantly different level (p<0.01) when rapidly versus slowly progressive cases of FTD were compared. Eleven peaks were expressed at different levels when high versus low CSF NF-L were compared. Using chromatographic purification followed by tandem mass spectrometric analysis, five of these peaks were identified as follows: C-terminal fragment of neuroendocrine protein 7B2 (3512.84 Da), C-terminal fragment of osteopontin (7658.19 Da) as well as its mono- and diphosphorylated forms (7738.16 Da and 7818.13 Da, respectively) and pancreatic ribonuclease (14566.33 Da). The peak intensity of pancreatic ribonuclease was higher in patients with low NF-L expression, while the other peptides had a lower peak intensity in this group. Altered levels of these peptides have also been described in other neurodegenerative diseases. Taken together, these data suggest that differentially-expressed peptides are general markers of axonal degeneration. Further studies are needed to verify their prognostic value in FTD.
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| 41. |
- Ungerbäck, Jonas, et al.
(författare)
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Analysis of VEGF polymorphisms, tumor expression of VEGF mRNA and colorectal cancer susceptibility in a Swedish population
- 2009
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Ingår i: MOLECULAR MEDICINE REPORTS. - : Spandidos Publications. - 1791-2997. ; 2:3, s. 435-439
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) plays a significant role in tumor angiogenesis and is found to be overexpressed and involved in the development and progression of colorectal cancer (CRC). The VEGF gene contains several polymorphic sites known to influence VEGF expression. We examined the possible association between five polymorphisms, located in the promoter/5-untranslated region [-2578 (C/A), -2549 (del/ins 18 bp) -1154 (G/A), -634 (G/C)] or 3-untranslated region [+936 (C/T)] of the VEGF gene, and CRC Susceptibility and clinicopathological characteristics in 302 Swedish CRC patients and 336 healthy randomly selected controls. Both genotypes and combined haplotypes were analyzed. No significant differences were observed when VEGF genotype/haplotype frequencies in the CRC cases and controls were compared, nor were any associations found between the genotypes/haplotypes and clinicopathological characteristics. However, when the -2578 C and +936 T alleles were combined, a small but significant association with CRC susceptibility was detected (OR=1.6, 95% CI 1.3-1.9, p=0.01). In addition, VEGF mRNA expression was determined in a Subset of patients, revealing a 2-fold VEGF upregulation in CRC tissue compared to normal colonic mucosa, but no association between the genotypes or haplotypes and VEGF mRNA levels. Linkage analysis was performed, revealing that the polymorphisms in the promoter and 5-untranslated region were in tight linkage disequilibrium (LD) (vertical bar Dvertical bar=0.91-1.00), while the +936 C/T polymorphism was only weakly associated with the others (vertical bar Dvertical bar=0.05-0.19). In conclusion, VEGF is generally upregulated in colorectal tumors. However, the single nucleotide polymorphisms examined do not appear to influence the mRNA expression of VEGF in colorectal tumors, and most likely play a limited role in CRC development and progression.
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| 42. |
- Wang, Min, et al.
(författare)
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Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways
- 2019
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Ingår i: Molecular Medicine Reports. - 1791-2997. ; 19:2, s. 1272-1283
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Spandidos Publications. All rights reserved. Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high-density lipoprotein (HDL) decreases inflammatory responses via the apoM-sphingosine-1-phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM-/-) were employed to investigate the effects of ApoM on the expression of interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1), S1P receptor-1 (S1PR1) and 3β-hydroxysterol Δ-24-reductase (DHCR24), as compared with in wild-type mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (rec-apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor-α (TNF-α), in order to investigate the effects of ApoM on IL-1β and MCP-1. The results demonstrated that the mRNA expression levels of IL-1β and MCP-1 were significantly higher in the liver following administration of lipopolysaccharide in apoM-/- mice compared with in apoM+/+ mice. In cell culture experiments, when cells were pre-cultured with rec-apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL-1β and MCP-1 following TNF-α treatment compared with in normal apoM-expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL-1β and MCP-1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport-1 (BLT-1), in apoMTg cells prior to TNF-α treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT-1 prior to TNF-α treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways.
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